1-9246952-T-TC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_004285.4(H6PD):c.628-6dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000771 in 1,554,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (0 hom.)
• Consequence: H6PD NM_004285.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

Genes affected

H6PD (HGNC:4795): (hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase) There are 2 forms of glucose-6-phosphate dehydrogenase. G form is X-linked and H form, encoded by this gene, is autosomally linked. This H form shows activity with other hexose-6-phosphates, especially galactose-6-phosphate, whereas the G form is specific for glucose-6-phosphate. Both forms are present in most tissues, but H form is not found in red cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-9246952-T-TC is Benign according to our data. Variant chr1-9246952-T-TC is described in ClinVar as [Benign]. Clinvar id is 3022168.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H6PD	NM_004285.4	c.628-6dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000377403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H6PD	ENST00000377403.7	c.628-6dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004285.4	P1
H6PD	ENST00000602477.1	c.661-6dup		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.000524 AC: 79 AN: 150826 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000391

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.000630

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000694

Gnomad OTH AF: 0.000483

GnomAD4 exome AF: 0.000797 AC: 1119 AN: 1403976 Hom.: 0 Cov.: 26 AF XY: 0.000813 AC XY: 570 AN XY: 701220

Gnomad4 AFR exome AF: 0.000864

Gnomad4 AMR exome AF: 0.000630

Gnomad4 ASJ exome AF: 0.000117

Gnomad4 EAS exome AF: 0.00116

Gnomad4 SAS exome AF: 0.000937

Gnomad4 FIN exome AF: 0.000631

Gnomad4 NFE exome AF: 0.000791

Gnomad4 OTH exome AF: 0.000945

GnomAD4 genome AF: 0.000530 AC: 80 AN: 150940 Hom.: 0 Cov.: 32 AF XY: 0.000489 AC XY: 36 AN XY: 73612

Gnomad4 AFR AF: 0.000414

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00137

Gnomad4 SAS AF: 0.000630

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000694

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.000552

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 16, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201586222; hg19: chr1-9307011;